Abstract

Background:
Chronic hyperglycemia has been hypothesized to contribute to coronary heart disease (CHD), but the extent to which hemoglobin A(1c) (HbA(1c)) level, a marker of long-term glycemic control, is independently related to CHD risk is uncertain.

Methods:
We conducted a prospective case-cohort study of 1321 adults without diabetes and a cohort study of 1626 adults with diabetes from the Atherosclerosis Risk in Communities Study. Using proportional hazards models, we assessed the relation between HbA(1c) level and incident CHD during 8 to 10 years of follow-up.

Results:
In adults with diabetes, the relative risk (RR) of CHD was 2.37 (95% confidence interval [CI], 1.50-3.72) for the highest quintile of HbA(1c) level compared with the lowest after adjustment for CHD risk factors. In persons without diabetes, the adjusted RR of CHD in the highest quintile of HbA(1c) level was 1.41 (95% CI, 0.90-2.30); however, there was evidence of a nonlinear relationship in this group. In nondiabetic adults, HbA(1c) level was not related to CHD risk below a level of 4.6% but was significantly related to risk above that level (P<.001). In diabetic adults, the risk of CHD increased throughout the range of HbA(1c) levels. In the adjusted model, the RR of CHD for a 1-percentage point increase in HbA(1c) level was 2.36 (95% CI, 1.43-3.90) in persons without diabetes but with an HbA(1c) level greater than 4.6%. In diabetic adults, the RR was 1.14 (95% CI, 1.07-1.21) per 1-percentage point increase in HbA(1c) across the full range of HbA(1c) values.

Conclusion:
Elevated HbA(1c) level is an independent risk factor for CHD in persons with and without diabetes.